doi:10.1111/jog.13809 J. Obstet. Gynaecol. Res.

2018

First trimester screening for preterm and term

pre-eclampsia by maternal characteristics and biophysical
markers in a low-risk population

Alvaro Sepúlveda-Martínez1, Gustavo Rencoret2, María C. Silva1, Paz Ahumada3,

Daniel Pedraza1, Hernán Muñoz1, Enrique Valdés1 and Mauro Parra-Cordero1,2
Departments of Obstetrics and Gynecology 1Fetal Medicine Unit Hospital Clínico Universidad de Chile, 2Fetal Medicine Unit
Hospital San Borja Arriarán and 3Faculty of Medicine, Universidad de Chile, Santiago de Chile, Chile

Abstract
Aim: To develop a combined predictive model for preterm and term pre-eclampsia (PE) during the first tri-
mester of pregnancy.
Methods: This investigation was a nested case–control study in singleton pregnancies at the Maternal-Fetal
Medicine Unit, University of Chile Hospital. A priori risks for preterm and term PE were calculated by multi-
variate logistic regression analyses. Biophysical markers were log10-transformed and expressed as multiples
of the median. A multivariate logistic regression analysis was used to estimate a combined predictive model
of preterm and term PE. Detection rates at different cut-off points were determined by a receiver operator
curve analysis of a posteriori risks.
Results: First trimester mean arterial pressure and uterine artery Doppler pulsatility index were significantly
higher in women who develop PE than in the unaffected group. The detection rate of preterm PE based on
maternal characteristics and biophysical markers was 72% at a 10% false-positive rate, corresponding to a
cut-off risk of 1 in 50. The detection rate for term PE was 30% at a 10% false-positive rate.
Conclusion: Preterm PE can be predicted by a combination of maternal characteristics and biophysical
markers. However, first trimester screening is less valuable for term PE.
Key words: Doppler, first trimester, mean arterial pressure, prediction, pre-eclampsia, uterine artery.

Introduction Thus far, several meta-analyses and a recent random-

Pre-eclampsia (PE) is one of the main causes of mater-
nal morbidity and mortality in developed countries.1
In Chile, pregnancy-associated hypertension repre-
sents the second cause of maternal death, according
to the last national report.2
From a public health point of view, the develop-
ment of a predictive model of PE is of major interest
to establishing a universal screening program. How-
ever, the identification of a high-risk population needs
a low-cost preventive strategy to be cost-effective.
ized controlled trial have proven that high-risk popu-
lations could benefit from the use of aspirin started
before 16 weeks of gestation.3–6
Although the performance of a screening test for PE
in the second trimester of pregnancy is the best
approach,7 an earlier assessment might ensure a
reduction in the risk of PE in women who develop
this condition. In this vein, several first trimester pre-
dictive models have been published, requiring a com-
bination of maternal history, biochemical markers and
uterine artery Doppler (UtAD).5,8–13 At a fixed false-

Received: March 27 2018.

Accepted: August 10 2018.
Correspondence: Dr Mauro Parra-Cordero, Fetal Medicine Unit, Department of Obstetrics and Gynecology, Hospital Clínico
Universidad de Chile, Santos Dumont 999 Sector A Primer Piso, Independencia, Santiago de Chile, Chile. Email: mcparra@hcuch.cl

© 2018 Japan Society of Obstetrics and Gynecology 1

A. Sepúlveda-Martínez et al.
positive rate of 10%, the detection rates (DR) vary,
depending on the population, from 47% to 96%.8,14
Interestingly, the incorporation of the mean arterial
pressure (MAP) at the first trimester screening has
been demonstrated to improve the DR of these
models.
The aim of this study was to develop a first trimes-
ter combined predictive model for preterm and term
PE that includes maternal history and biophysical
markers.
Methods
Study design
This was a nested case–control study within an ongo-
ing 11 + 0 to 13 + 6 weeks screening program at the
Fetal Medicine Unit, University of Chile Hospital,
from November 2010 to January 2017. At the appoint-
ment, all patients were offered a risk assessment for
PE and chromosomal abnormalities that included
maternal characteristics, medical and obstetrics his-
tory and an assessment of MAP and transvaginal
UtAD. Gestational age was calculated by crown-to-
rump length (CRL) in all pregnancies.15
Perinatal outcomes were obtained from the labor
and delivery unit or by phone contact with patients
who delivered in another institution. This study was
approved by the local Ethics Committee of Hospital
Clínico de la Universidad de Chile (Registry No. 57)
and was funded by Fondo Nacional de Desarrollo
Científico y Tecnológico (FONDECYT) (Registry
No. 1130668).
Patient selection
For this study, only singleton pregnancies with a com-
plete screening and known perinatal outcome were
included. Patients with spontaneous abortion before
22 weeks of gestation, the presence of aneuploidy
diagnosed prenatally or after delivery or a major birth
defect were excluded from the analysis. Genetic syn-
dromes diagnosed after birth were also excluded. All
patients who agreed to participate signed a written
informed consent.
Definitions
For this study, PE was defined as hypertension devel-
oping after 20 weeks of gestation and proteinuria
≥300 mg/day (or spot urine protein/creatinine ratio
≥30 mg/mmol or dipstick 2+) in a previously normo-
tensive patient, according to the revised statement of
2 © 2018 Japan Society of Obstetrics and Gynecology
the International Society for the Study of Hyperten-
sion in Pregnancy.16 Preterm PE (p-PE) and term PE
(t-PE) were defined as individuals with PE who deliv-
ered before and after 37 weeks of gestation,
respectively.
Small for gestational age (SGA) was defined as a
birthweight <10th percentile, according to local stan-
dards.17 Fetal growth restriction (FGR) was defined as
SGA with altered Doppler, SGA delivered before
37 weeks of gestation due to fetal or maternal condi-
tion, or a birthweight less than 3rd percentile, irre-
spective of Doppler status or gestational age at
birth.18
Maternal characteristics
All pregnant women were asked to complete an oral
questionnaire, which was stored in our Astraia (r)
database. The maternal characteristics included were
maternal age, mode of conception (spontaneous or
assisted reproductive technology), maternal height,
maternal weight before pregnancy and at ultrasound,
body mass index (BMI), ethnicity, smoking habit (yes
or no), previous PE (yes or no), previous SGA new-
born (yes or no), birthweight of previous pregnancy,
previous spontaneous preterm delivery (yes or no)
and background of chronic diseases, including the fol-
lowing: chronic hypertension (chrHT) (yes or no),
autoimmune diseases (yes or no) and diabetes melli-
tus 1 or 2 (yes or no).
Biophysical markers
Blood pressure was assessed twice in both arms in all
patients, according to the Seventh Joint National
Committee (JNC-7) recommendations19 using an
automatic validated tensiometer (OMRON HEM-
7113, Omron Healthcare Inc.). MAP was calculated as
follows: MAP = DBP + (SBP-DBP)/3, with MAP as
the mean arterial pressure, DBP as the diastolic blood
pressure and SBP as the systolic blood pressure.
The transvaginal UtAD was measured using an
Accuvix A30 (Samsung Medison) or Aloka 4000
(Aloka) machine with a 5–8 MHz endo-cavitary
probe. The technique used was as follows: Patients
were placed in lithotomy position, and the transducer
was introduced into the vagina and placed at the
anterior fornix. After identification of the cervix, the
transducer was tilted laterally, at the level of the inter-
nal os. Color Doppler was used to identify left and
right uterine arteries. Pulsed Doppler was used after
confirmation of an insonation angle <30
. When three
consecutive similar waves were obtained, the image

was stored, and the pulsatility index (PI) was calcu-
lated.20 The mean PI of the left and right UtAD was
calculated and stored.
Study outcomes
The primary outcome was the diagnosis of p-PE with
or without FGR. The secondary outcome was the
diagnosis of t-PE.
Statistical analysis
All statistical analyses were performed with STATA
v14.2 software (Statacorp). For continuous variables,
Student’s t-test or the Mann–Whitney U test was used
and expressed as the mean (standard deviation) or
median (interquartile range [IQR]) for parametric and
nonparametric distributions, respectively. Categorical
variables were compared with Pearson’s chi-square
test and expressed as n (%). For the analysis of predic-
tive variables, a Bayes theorem approach was used.
A priori risk
First, maternal characteristics were explored with a
univariate logistic regression analysis to determine
the odds ratios (OR) of variables significantly associ-
ated with the primary outcome. Second, a multivari-
ate logistic regression analysis was applied, using a
backward stepwise elimination method. Variables
with a P value less than 0.05 were retained in the final
model. Finally, to determine the individual risk, odds
were calculated as follows: Odds = ey. Then, risk was
estimated as follows: Odds/(1 + Odds). The a priori
risk was log10-transformed before including in the a
posteriori risk model.
Biophysical predictor markers
First, MAP and UtAD were log10-transformed to
make their distribution Gaussian. Second, a multivari-
ate linear regression was performed to identify which
variables were significant predictors of log10MAP and
log10UtAD in the unaffected group. The obtained
regression was used to determine multiples of the
median (MoM) of both markers. For missing values of
UtAD measurements in 14 controls, a multiple impu-
tation analysis of missing values was performed.
A posteriori risk
To determine the a posteriori risk, a multivariate logis-
tic regression was applied, combining the a priori
risk(log10), MoM-MAP and MoM-UtAD. A receiver
operator curve analysis was performed to determine
the DR at a fixed false-positive rate of 10%. The
© 2018 Japan Society of Obstetrics and Gynecology
First trimester prediction of preterm pre-eclampsia
obtained regression formula was used to determine
the individual risk, in the same manner as a priori risk
estimation. Finally, the DR at different a posteriori risk
cut-offs was estimated.
For group comparison, a P value less than 0.05 was
considered significant.
Results
During the study period, we included 1812 patients.
Of these, 56 were excluded for spontaneous miscar-
riage (30), stillbirth (8), neonatal death related to
major congenital defect (4) and live birth with a major
congenital defect (14). After exclusion, 1756 singleton
pregnancies were included in the final analysis. Forty-
nine (2.8%) patients developed PE, and 29 of them
were delivered before 37 weeks of gestation. Maternal
characteristics and the obstetric history of the study
population are presented in Table 1. Patients who
subsequently developed PE were older and heavier
and had higher rates of smoking and chrHT than
patients with unaffected pregnancies. There were no
differences in ethnicity, with a predominance of the
white Hispanic population in both groups. Twenty-
nine percent of patients in the PE group had a history
of PE in a previous pregnancy, compared to 2.5% of
patients in the unaffected group (P < 0.0001).
At screening, pregnancies that developed PE pre-
sented a significantly higher SBP and DBP, with a
MAP of 85 mmHg (78.8–93.3) and 80 mmHg
(73.3–86.3) in the PE and unaffected groups, respec-
tively (Table 2). The mean UtAD was also higher in
the PE group, with an almost threefold higher rate of
pregnancies with a PI above the 90th percentile. Peri-
natal outcomes are presented in Table 2.
A priori risk
A univariate logistic regression model was performed
to identify the maternal characteristic risk factors for
p-PE and t-PE. Regarding p-PE risk factors, chrHT
(OR = 13), systemic lupus erythematosus (SLE)
(OR = 8), previous history of PE (OR = 27), SGA
(OR = 12) and spontaneous preterm delivery
(OR = 8) presented higher risk. However, after a mul-
tivariate analysis, only chrHT, SLE and a previous
history of PE were retained in the model (Table 3).
For t-PE, only BMI and smoking habit were associ-
ated with a modest but significantly higher risk.
The a priori risk for p-PE was obtained with the fol-
lowing formula:
3
A. Sepúlveda-Martínez et al.

Table 1 Maternal characteristics and obstetric history of study population†

Characteristics Unaffected (n = 1707) Pre-eclampsia (n = 49) P value
Maternal background
Maternal age (years) 30 (26–35) 33 (29–36) 0.02
Chronic hypertension 56 (3.3) 10 (20.4) <0.0001
Diabetes mellitus 1 or 2 11 (0.6) 1 (2.0) 0.29
Systemic lupus erythematosus 15 (0.9) 2 (4.1) 0.08
Antiphospholipid syndrome 6 (0.4) 0 1.0
Smoking habit 151 (8.9) 10 (20.4) 0.006
Height (cm) 160 (156–164) 160 (157–165) 0.5
Weight (kg) 65 (58–75) 71 (64–76) 0.005
Body mass index (kg/m2) 25.4 (23.0–29.3) 27.3 (25.5–30.1) 0.005
Ethnicity
Caucasian 60 (3.5) 2 (4.1) 0.76
Hispanic-white 1639 (96) 47 (95.9)
Hispanic-black 2 (0.1) 0
Other 6 (0.4) 0
Obstetric history
Nulliparity 779 (45.6) 18 (36.7) 0.2
Previous PE 43 (2.5) 14 (28.6) <0.0001
Previous SGA 16 (0.9) 2 (4.1) 0.06
Previous sPTD 61 (3.6) 5 (10.2) 0.05
Family history of PE (mother) 39 (2.3) 1 (2.0) 1.0
Type of conception
Spontaneous 1672 (97.9) 48 (98.0) 1.0
ART 35 (2.1) 1 (2.0)
†Continuous data are expressed as median (interquartile range) and categorical data are expressed as n (%). ART, assisted reproductive
technology; PE, pre-eclampsia; SGA, small for gestational age; sPTD, spontaneous preterm delivery.

y ¼ − 5:354954 + maternal age × 0:0218775 comparison to unaffected pregnancies (unaffected
+ ð1:534937 ½if chrHTÞ + ð2:026845 ½if SLE pregnancies 1.001 [0.983–1.017]; t-PE 1.005
[0.983–1.020]; and p-PE 1.015 [0.998–1.027]; P = 0.02).
+ ð0 ½if nulliparousÞ
In addition, in the unaffected pregnancies, the mean
– ð0:1196494 ½if parous without previous PEÞ UtAD PIlog10 was better predicted with the following
+ ð2:754261 ½if parous with previous PEÞ formula:

The a priori risk for t-PE was obtained with the fol- y ¼ 0:4190377 – ð0:0025075 × CRLÞ
lowing formula:  

– 0:0029433 × maternal age years
+ ð0 ½if nulliparous + 0:0015571
y ¼ − 6:942792 + ð0:0832792 × BMIÞ
 
½if parous without previous PE
+ 1:254454 if smoking habit
+ 0:0794263 ½if parous with previous PE

Figure 1b shows that there was an increased

Biophysical markers
In the unaffected group, MAPlog10 was better pre-
dicted with the following formula:
 

y ¼ 1:77849 + 0:0006087 × maternal age years
 

+ ð0:0038327 × BMIÞ – 0:0080398 if smoking habit
+ ð0:0475634 ½if chrHTÞ
Figure 1a shows that there was an increased MoM-
MAP in the pregnancies that developed p-PE in
MoM-UtAD only in pregnancies that later devel-
oped p-PE in comparison to unaffected pregnancies
(unaffected pregnancies 1.012 [0.827–1.210]; t-PE
1.139 [0.951–1.353]; p-PE 1.314 [1.129–1.445];
P = 0.0008).
As presented in Figure 2, first trimester MoM-MAP
and MoM-UtAD were inversely and significantly cor-
related with gestational age at delivery (r = −0.1016;
P < 0.0001 and r = −0.1377; P < 0.0001, respectively,
for global PE).

4 © 2018 Japan Society of Obstetrics and Gynecology

 First trimester prediction of preterm pre-eclampsia

Table 2 First trimester screening characteristics and perinatal outcome†

Characteristics Unaffected (n = 1707) Pre-eclampsia (n = 49) P value
11 + 0 to 13 + 6 weeks screening
Crown-to-rump length (mm) 66 (59–73) 65 (58–69) 0.17
Mean UtA Doppler PI 1.48 (1.22–1.8) 1.93 (1.49–2.2) <0.0001
Mean UtA Doppler > p90 121 (7.2) 10 (20.4) 0.007
Mean SBP (mmHg) 105.5 (98.3–115) 113 (105–124) 0.0004
Mean DBP (mmHg) 66.5 (60.0–72.5) 70.0 (64.5–80.0) 0.0025
Mean arterial pressure (mmHg) 80.0 (73.3–86.3) 85 (78.8–93.3) 0.0004
Perinatal outcome
Placental abruption 5 (0.3) 3 (6.3) 0.001
Cesarean section rate 904 (53.8) 42 (87.5) <0.0001
Stillbirth 3 (0.2) 1 (2.0) 0.11
Gestational age at birth (weeks) 39.0 (38.2–39.8) 36.5 (32.9–37.5) <0.0001
Preterm delivery‡
Less than 34 weeks 32 (2.0) 16 (44.4) <0.0001
Less than 37 weeks 153 (9.0) 29 (59.2) <0.0001
Birthweight, grams 3380 (3065–3690) 2500 (1700–3090) <0.0001
Birthweight percentile 54.1 (33.6–75.9) 21.8 (7.9–46.3) <0.0001
Small for gestational age
Less than 10th percentile 71 (4.2) 14 (29.2) <0.0001
Less than 3rd percentile 18 (1.1) 4 (10.5) 0.001
FGR 33 (2.0) 11 (24.4) <0.0001
Male sex 839 (50.0) 24 (49.0) 0.90
5-min Apgar score <7 12 (0.8) 3 (6.8) 0.007
†Continuous data are expressed as median (interquartile range) and categorical data are expressed as n (%).; ‡Spontaneous and iatrogenic
combined. DBP, diastolic blood pressure; FGR, fetal growth restriction; SBP, systolic blood pressure; UtA, uterine artery.

Combined predictive model for PE curve [AUC]: 0.817 [0.725–0.908]). Following the inclu-
For p-PE, at a fixed false-positive rate of 10%, the DR sion of MoM-MAP and MoM-UtAD, the DR of the
based on a priori risklog10 was 62.1% (area under the model went up to 72.4% (AUC: 0.890 [0.837–0.955];

Table 3 Odds ratios for significant maternal characteristics after univariate and multivariate logistic regression analysis
Maternal characteristics Univariate regression Multivariate regression
OR (95% CI) P value OR (95% CI) P value
Preterm PE
Chronic hypertension 13.3 (5.78–30.44) <0.0001 4.9 (1.78–13.41) 0.002
SLE 8.4 (1.82–38.34) 0.006 7.5 (1.13–49.13) 0.037
Previous PE
Nulliparous Reference — Reference —
Parous no previous PE 0.99 (0.38–2.58) 0.98 0.98 (0.37–2.59) 0.97
Parous with previous PE 27.2 (10.55–69.97) <0.0001 17.2 (5.96–49.53) <0.0001
Previous SGA
Nulliparous Reference — Excluded† —
Parous no previous SGA 2.0 (0.88–4.66) 0.10
Parous with previous SGA 12.2 (2.39–61.91) 0.003
Previous sPTD
Nulliparous Reference — Excluded† —
Parous no previous sPTD 1.8 (0.76–4.19) 0.18
Parous with previous sPTD 8.0 (2.52–25.04) <0.0001
Term pre-eclampsia
Maternal weight (kg) 1.03 (1.00–1.06) 0.029 Excluded† —
Body mass index (kg/m2) 1.08 (1.01–1.17) 0.036 1.1 (1.01–1.17) 0.035
Smoking habit 3.4 (1.23–9.58) 0.018 3.5 (1.25–9.81) 0.017
†Variable excluded after multivariate regression analysis. CI, confidence interval; OR, odds ratio; PE, pre-eclampsia; SGA, small for gesta-
tional age; SLE, systemic lupus erythematosus; sPTD, spontaneous preterm delivery.

© 2018 Japan Society of Obstetrics and Gynecology 5

A. Sepúlveda-Martínez et al.

Figure 1 Boxplot of multiples of the median (MoM) for mean arterial pressure (MAP) and uterine artery Doppler (UtAD) at first
trimester scan. (a) MoM of MAP; (b) MoM of UtAD pulsatility index. PE, preeclampsia. *P value < 0.05 versus unaffected.

Figure 2 Scatter plot of

first-trimester biophysical
markers according to ges-
tational age at delivery.
(a) multiples of the
median (MoM) of mean
arterial pressure (MAP);
(b) MoM of uterine artery
Doppler (UtAD). PE, pre-
eclampsia. *P value < 0.05
versus unaffected.

Figure 3). The following formula represented the best
predictive model for p-PE:
 
y ¼ − 5:117278 + 2:777415 × a priori risk log10
+ ð3:487746 × MoM − MAPÞ
+ ð2:158282 × MoM − UtADÞ
With regard to t-PE, at a fixed false-positive rate of
10%, the DR based on a priori risklog10 was 30.0%
(AUC: 0.690 [0.580–0.799]). However, both MoM-
MAP and MoM-UtAD were not significantly associ-
ated with t-PE and were therefore not included in the
final model.
Table 4 shows the DR and false-positive rates of dif-
ferent a posteriori risk cut-offs for p-PE. At a cut-off risk
of 1 in 100, 27.2% of pregnancies were classified as
high-risk but with a 25.7% false-positive rate. To reduce
the false-positive rate without significantly affecting the
DR, a cut-off risk of 1 in 50 might be considered more
appropriate for our population, due to the fact that
only 7.8% were classified as high-risk pregnancies with
a 72% DR and only a 10.4% false-positive rate.

6 © 2018 Japan Society of Obstetrics and Gynecology

 First trimester prediction of preterm pre-eclampsia

Strengths and limitations

To our knowledge, the main strength of our study
was being the first predictive model for p-PE devel-
oped in a Latin American population at the 11 + 0 to
13 + 6 weeks scan, which combines maternal charac-
teristics with adjusted biophysical markers in a clini-
cal setting. An algorithm was provided to compare
our model with already validated models applied in a
clinical setting in our population. Second, the use of a
validated and well-described methodology for the
adjustment of biophysical markers, expressed as
MoM, allows our results to be compared with those
of other publications. Additionally, the use of a Bayes-
ian theorem approach for a priori and a posteriori risk
estimation allows for an individualized assessment
and management, based on predefined cut-off points.
Finally, the use of a clinical and research-dedicated
database, with a prospective collection of perinatal
outcomes, ensures the quality of our data.
Figure 3 Receiver operator curves of a priori and com-
However, this study is not without limitations. First,
bined for preterm PE. The dashed line (---) represents we did not evaluate any angiogenic/anti-angiogenic
the prediction for a priori risk, and the continuous line marker in maternal plasma, such as placental growth
(─) represents the combined model: a priori + multiples factor (PLGF) or pregnancy-associated protein plasma
of the median (MoM)-mean arterial pressure (MAP) + A. Therefore, the real impact of these markers in our
MoM-uterine artery Doppler (UtAD). The vertical dot-
ted line represents a 10% false-positive rate.
population is unknown, despite a good DR with the
present model, similar to other publications.11,21 Sec-
ond, we acknowledge that this study was performed in
Discussion a tertiary center by experts with major experience in
first trimester ultrasound, affecting the external valida-
Main findings
tions of our results. In this vein, the need to validate
This study corroborates that a first trimester predic- this model and compare its performance with a more
tive model of PE that combines maternal characteris- robust already published model, such as the Fetal Med-
tics and biophysical markers, such as MAP and icine Foundation algorithm21 appears to be mandatory
UtAD, can detect a high proportion of pregnancies in the near future. Third, considering that the use of
destined to develop PE before 37 weeks of gestation, aspirin from the first trimester could affect the results
with a 10% false-positive rate. However, the DR of t- of our model, we did not have data in all patients
PE appears to be poorer at this gestational age, and regarding this use. Therefore, a statistical adjustment
particularly, the biophysical markers were not associ- was not feasible to perform. Finally, it is important to
ated with this subtype of PE. consider that the high false-positive rate for different
cut-offs that we described might be influenced by our
particular ethnicity, which is a mixture of native-
Table 4 Detection and false-positive rates for preterm
pre-eclampsia at different a posteriori risk cut-offs American and European population22 and by the possi-
ble use of aspirin and lack of adequate adjustment.
A posteriori Detection False LHR+ LHR−
risk cut-off rate (%) positive
rate (%)
Interpretation
1 in 50 72.4 10.4 6.9 0.3
1 in 85 82.8 20.0 4.1 0.2 The high DR of p-PE based on a priori risk (62.1%)
1 in 100 89.7 25.7 3.5 0.1 could be explained by local population characteristics,
1 in 150 96.6 43.6 2.2 0.1 where 3.8% of the screened population have a back-
1 in 200 96.6 58.9 1.6 0.1 ground of chronic hypertension, and 5.9% of parous
LHR, Likelihood ratio. females have developed PE in a previous pregnancy.

© 2018 Japan Society of Obstetrics and Gynecology 7

A. Sepúlveda-Martínez et al.
However, Wright D et al. described that in parous
patients, a priori risk detected 61.7% of p-PE at a 10%
false-positive rate, which is similar to our findings.11
Regarding the performance of combined models, in
a recent study, O’Gorman et al. screened 35 948 sin-
gleton pregnancies at 11 + 0 to 13 + 6 weeks. They
demonstrated that by combining maternal characteris-
tics, MoM-UtAD and MoM-MAP, the DR of p-PE was
70% (95% confidence interval 64–75) at a 10% fixed
false-positive rate.21 The inclusion of PLGF into the
predictive model marginally improved the DR to
75%. Moreover, our group published that adding
PLGF into a predictive model can only increase the
DR in our population by three percentile points.14
Based on these findings and the eventual increase
in the cost by including biochemical markers in the
universal screening in our population, we believe that
a model that includes maternal characteristics and
biophysical markers has enough strength to detect the
vast majority of women who will benefit from taking
aspirin before 16 weeks of gestation.
Finally, from a clinical perspective, the algorithm
developed by the Fetal Medicine Foundation in a ran-
domized controlled trial demonstrated a 62% reduc-
tion of p-PE when 150 mg of aspirin was started at
11–14 weeks.5 However, a subanalysis demonstrated
that this benefit is not observed in chronically hyper-
tensive patients.23 In the abovementioned randomized
study, a cut-off risk of 1 in 100 was considered the
inclusion criteria, with values associated with a 10%
screen-positive rate. However, if a similar cut-off
point is used, more than 20% of our population
should be classified using the screen-positive rate,
which might reflect an inadequate overuse of aspirin.
Therefore, a cut-off risk of 1 in 50 should be more
suitable in our screening program to obtain a screen-
positive rate of approximately 10%.
In conclusion, we demonstrated that the use of a
first trimester model for the prediction of p-PE devel-
oped with a local population, could obtain similar DR
than international reports. However, t-PE might be
unlikely to be predicted properly during the first tri-
mester of pregnancy. Local risk cut-offs should be
selected before the implementation of preventive
strategies in a high-risk group.
Acknowledgments
We thank the administrative staff of the Fetal Medi-
cine Unit for their effort in obtaining perinatal
8 © 2018 Japan Society of Obstetrics and Gynecology
outcomes and contacting the patients. We also thank
the research midwife, Mrs Cristina Aleuanlli, for her
continuous help and energy in the development of
clinical research at our department. This study was
funded by Fondo Nacional de Desarrollo Científico y
Tecnológico (FONDECYT) Registry No. 1130668.
FONDECYT was not involved in the study design,
patient recruitment or data analysis.
Disclosure
None declared.
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